The immunological characterization of leukemic cells has facilitated investigations designed to improve our understanding of the heterogeneity and pathophysiology of acute leukemias. We have undertaken studies to characterize leukemic cell surface antigens with monoclonal and heteroantibodies. The monoclonal antibodies were prepared by somatic cell hybridization techniques. These antibodies have proven useful for the definition of both the heterogeneity and lineage of the leukemic cell and in defining its state of differentiation. The identification of unique antigens by serological techniques has allowed for the biochemical characterization of leukemic cell surface antigens. These studies have provided considerable insight into the nature of the leukemic process and the relationships of these leukemic cell surface antigens to those found during normal cellular differentiation. We have generated a series of antibodies to T cells, B cells, myeloid cells and monocytic cells for the classification and characterization of the acute and chronic leukemias in humans.